Quinoline derivatives represented by compound (IV):
are known to exhibit excellent antitumor activity (PTL 1).
PTLs 1, 2, 3, 4 and 5 disclose methods for producing these quinoline derivatives. Specifically, in the production method of PTL 1 (such as described in Example 368), 4-amino-3-chlorophenol hydrochloride is reacted with 4-chloro-7-methoxy-quinoline-6-carboxamide (step A), phenyl chloroformate is reacted with the obtained 4-(4-amino-3-chlorophenoxy)-7-methoxy-quinoline-6-carboxamide and the resulting phenyl N-{4-(6-carbamoyl-7-methoxy-4-quinolyl)oxy-2-chlorophenyl}carbamate is isolated (step B), and then cyclopropylamine is further reacted with the carbamate (step C) to obtain the target compound, 4-[3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy]-7-methoxy-6-quinoline-carboxamide (hereunder referred to as “compound (IV)”), with a total yield of 25.5% for the three steps.
In the production methods described in PTL 2 (Reference Example 1) and PTL 4 (Production Example 1), cyclopropylamine is reacted with phenyl N-{4-(6-carbamoyl-7-methoxy-4-quinolyl)oxy-2-chlorophenyl}carbamate to obtain compound (IV), with a yield of 80.2%.
In the production methods described in PTL 2 (Reference Example 3), PTL 3 (Example 4), PTL 4 (Production Example 3) and PTL 5 (Example 1a), the target compound (IV) is obtained by a single step from 4-chloro-7-methoxy-quinoline-6-carboxamide, with a yield of 86.3% in PTLs 2 to 4 and a yield of 91.4% in PTL 5.
Subsequently, the production methods described in PTLs 1 to 5 will be specifically described. The production method described in PTL 1 (Example 368 and the like) is as the following formulas.

The reaction scheme for the production method in PTL 2 (Reference Example 1) and PTL 4 (Production Example 1) is as follows.

The production methods in PTL 2 (Reference Example 3), PTL 3 (Example 4), PTL 4 (Production Example 3) and PTL 5 (Example 1a) have the following reaction scheme.
